Tetrabutylammonium Fluoride Trihydrate → (3R,4R)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-(isopropylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158441노트

반응식

HRID 1158441 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:24]([CH3:26])[CH3:25])C(OCC[Si](C)(C)C)=O)[C@H:10]([CH2:27][N:28]([CH:38]2[CH2:40][CH2:39]2)[C:29](=[O:37])[CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH:24]([CH3:25])[CH3:26])[C@H:10]([CH2:27][N:28]([CH:38]2[CH2:39][CH2:40]2)[C:29](=[O:37])[CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

참가 물질

4

반응물 2

HCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 59512347(3R,4S)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-{[isopropyl-(2-trimethylsilanyl-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 59512261(3R,4R)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-(isopropylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a solution of (3R,4S)-3-[(cyclopropyl-phenylacetyl-amino)-methyl]-4-{[isopropyl-(2-trimethylsilanyl-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (2.55 g, 4.44 mmol) in CH3CN (30 mL) is added tetrabutylammonium fluoride trihydrate (4.34 g, 13.33 mmol) under a nitrogen atmosphere. The reaction mixture is stirred overnight at reflux. The solvent is removed under vacuum and Water and CH2Cl2 are added, the layers are separated and the aqueous one extracted twice with CH2Cl2. The combined organic extracts are dried (Na2SO4), and the solvent is removed in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH 98:2:1) to give the title product. TLC, Rf (CH2Cl2/MeOH/NH4OH 98:2:1)=0.11. MS (LC-MS): 430.2 [M+H]+; tR (HPLC, C18 column, 20-100% CH3CN/H2O/16 min, 100% CH3CN/1.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 3.90 min.

후처리

  1. temperatureat reflux
  2. customThe solvent is removed under vacuum and Water and CH2Cl2
  3. additionare added
  4. customthe layers are separated
  5. extractionthe aqueous one extracted twice with CH2Cl2
  6. dry with materialThe combined organic extracts are dried (Na2SO4)
  7. customthe solvent is removed in vacuo
  8. customThe crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH 98:2:1)

출처 및 근거

ORD 기록
ord-6e29d67b35a7497dad7c002e31e38f03
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807709B2

반응 노트

불러오는 중…